Apparatus, System and Method for Precision Depth Measurement

ABSTRACT

Systems, apparatus, and methods are disclosed for locating tissue layer transitions within a cornea, including focusing a laser to a laser spot with an energy below a photodisruption threshold of the cornea, varying a position of the focal spot of the laser between an anterior surface of the cornea and a posterior surface of the cornea, and determining one or more transitions of the tissue layers based on a change in harmonic light generated by the laser spot.

BACKGROUND OF THE INVENTION

Field of the Invention

The present invention pertains generally to ophthalmic surgery, which isuseful for correcting vision deficiencies. More particularly, thepresent invention pertains to systems and methods for precise depthmeasurements of corneal layers within the eye.

Corneal shape corrective surgeries are commonly used to treat myopia,hyperopia, astigmatism, and the like. Procedures employing an excimerlaser include laser assisted in-situ keratomileusis (LASIK), photorefractive keratectomy (PRK) and laser sub-epithelial keratomileusis(LASEK). During LASIK, a suction ring is typically placed over scleratissue (the white part of the eye) to firmly hold the eye. Amicrokeratome with an oscillating steel blade can be used to make apartial incision through the front surface of a cornea and/or toautomatically pass across the cornea to create a thin flap of tissue onthe front central part of the eye. Alternatively, a femtosecond pulsedlaser beam may be used to create a corneal flap. After the suction ringis removed, the flap is lifted to expose tissue for ablation with alaser. The laser is typically programmed to correct a desired amount ofvisual effect, and directs a laser beam at the exposed tissue. A rapidemission of laser pulses removes very small precise amounts of cornealtissue. In LASIK, one objective is the removal of only stromal tissuewith the consequent preservation of anterior corneal tissue (e.g.,preservation of the epithelium and Bowman's layer). After irrigationwith saline solution, the corneal flap is folded back to heal in thepre-procedure or original position.

The flap incision is typically made to a depth below Bowman's layer, forexample, to ensure exposure of the stroma when the flap is lifted back.Bowman's layer may be difficult to identify, so many conventionalprocedures incise the flap at a pre-determined constant depth ordistance from the anterior surface of the cornea or optionally from anaplanation lens that might be used to contact the cornea. This depth ordistance may be derived from a historical or population based average ofcorneal thicknesses and may also include a buffer depth. Because somecorneas have an irregular thickness profile, some of these incisiondepths are conservatively pre-determined and can result in deepincisions into the stroma that incise more stromal tissue than istypically needed to form the flap. A remaining stromal layer (i.e., theflap bed following the flap incision) that is too thin may interferewith a desired ablation of the stroma for vision correction.

In light of the above, it would be desirable to provide systems,apparatus, and methods for accurately measuring depths within the corneafor vision correction procedures. It would also be desirable to provideaccurate depth measurements for use with producing corneal flapincisions below Bowman's layer while preserving or maximizing the amountof remaining stromal material (e.g., in the flap bed) for visioncorrection.

BRIEF SUMMARY OF THE INVENTION

Method, system, and apparatus are disclosed for locating tissue layertransitions within a cornea. A laser beam is focused to a laser spothaving an energy below a photodisruption threshold of the cornea, theposition of the laser spot is varied between an anterior surface of thecornea and a posterior surface of the cornea, and a transition of thetissue layers is determined based on a change in harmonic lightgenerated by the laser spot. The determination of one or more tissuelayer transitions can be used to calibrate the system, the laser beamfocus, and/or the position of the laser spot.

In one embodiment, a method of locating tissue layers within a cornea isprovided, the method including focusing a laser beam to a laser spothaving an energy below the photodisruption threshold of the cornea,varying a position of the laser spot between the anterior surface of thecornea and the posterior surface of the cornea, and determining atransition of the tissue layers based on a predetermined change in aharmonic signal. The laser beam has a pre-determined wavelength, and theharmonic signal, based on the pre-determined wavelength, is produced asthe laser spot propagates in the cornea.

In another embodiment, a system is provided for locating tissue layertransitions within a cornea. The system includes a laser subsystemconfigured to scan a laser spot between the anterior surface of thecornea and the posterior surface of the cornea, a sensor configured todetect a harmonic signal, and a processor coupled to the sensor and thelaser subsystem. The laser spot has an energy below the photodisruptionthreshold, and the harmonic signal is produced as the laser spotpropagates in the cornea. The processor is configured to monitor alocation of the laser spot within the cornea, measure a predeterminedchange in the harmonic signal, and correlate the location of the laserspot within the cornea with the change in the harmonic signal todetermine a tissue layer transition within the cornea.

In another embodiment, an apparatus is provided for determining a depthmeasurement and incising a cornea. The apparatus includes a first inputoperable to receive a first input signal indicating a focal depth of alaser beam within the cornea, a second input operable to receive asecond input signal representing a harmonic of the laser beam generatedas the laser beam propagates in the cornea, an output, and a processorcoupled to the first input, the second input, and the output. The laserbeam has an energy below the photodisruption threshold. The processor isconfigured to detect a pre-determined change in the second input signal,correlate the focal depth of the laser beam with a tissue layertransition to provide a reference depth of the laser beam, and transmitan output signal via the output, the output signal indicating thereference depth of the laser beam. The pre-determined change indicatesthe tissue layer interface within the cornea.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, wherein like reference numerals refer to similarcomponents:

FIG. 1 is a cross-sectional view of a portion of an eye showinganatomical layers of a cornea and a laser system for corneal layeridentification and precision depth measurement in accordance with oneembodiment;

FIG. 2 is a graph of intensity versus position illustrating arelationship of intensity change in a harmonic signal as a function offocal depth within corneal tissue;

FIG. 3 is a schematic diagram of the laser system used in situ while theeye is in contact with an aplanation lens in accordance with anotherembodiment;

FIG. 4 is a top view of a corneal flap mapped onto a cornea inaccordance with one embodiment;

FIG. 5 is a block diagram of a laser system in accordance with anotherembodiment;

FIG. 6 is a cross-sectional view of the portion of the eye shown in FIG.1 showing a diagnostic beam scanning the cornea; and

FIG. 7 is a cross-sectional view of the portion of the eye shown inFIGS. 1 and 6 showing a surgical beam incising a flap.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides systems, apparatus, and methods forprecision depth measurements within the eye, particularly the cornea. Inone embodiment, a femtosecond laser is used to output a beam having apredetermined wavelength to generate a harmonic thereof when propagatingin the corneal tissue. For depth measurement purposes, the beampreferably has an energy below a photodisruption threshold associatedwith the corneal tissue. The focal spot of the beam is scanned atvarying depths within the cornea, and the intensity of the harmonic isdetected and monitored for predetermined changes. These changescorrespond with tissue interfaces in the cornea and can be used toprecisely located tissue layers within the cornea, calibrate the focaldepth of the beam, determine the thickness of various tissue layers ofthe cornea, create two or three dimensional maps of the corneal tissue,and the like. Additionally, this information can be further used toprecisely locate incisions formed by the beam.

In some vision correction surgeries, the cornea is incised to form acorneal flap and expose the stroma (e.g., the flap bed being a stromalbed) for refractive correction. The depth of the flap incision ispreferably selected to preserve stroma for photoalteration (e.g., suchas ablation in laser vision correction surgery) or other modificationsto the stroma to effect refractive correction. For example, the averagethickness of the cornea is approximately 500 microns at the center ofthe cornea, the average thickness of the stroma is approximately 450microns at the center of the cornea (e.g., accounting for approximately90% of the cornea), the average thickness of the epithelium isapproximately 50 microns, and the average thickness of Bowman's layer isapproximately 10 microns. Some conventional femtosecond lasers have anaverage spot size of about 1 micron, which is insignificant with respectto the average thickness of the stroma. Using the systems, apparatus,and methods of the present invention, corneal incisions may be preciselylocated to maximize stroma preservation for subsequent modifications.

FIG. 1 is a cross-sectional view of a portion of an eye 10 showinganatomical layers of a cornea 12 and a system 23 for corneal layeridentification and precision depth measurement in accordance with oneembodiment. In general, the cornea 12 includes five anatomical layers oftissue (not drawn to scale) including the epithelium 14, Bowman's layer16, the stroma 18, Descemet's membrane 20, and the endothelium 22.Portions of the stroma 18 are typically removed during laser visioncorrection of the patient's vision (e.g., laser assisted in-situkeratomileusis (LASIK), photo refractive keratectomy (PRK), lasersub-epithelial keratomileusis (LASEK), and the like). The eye 10 alsohas an anterior chamber 24 cavity filled with aqueous humor 26, and thepressure exerted by the aqueous humor 26 generally maintains the shapeof the cornea 12.

The system 23 includes a controller 25, a laser subsystem 28 (e.g., afemtosecond laser) coupled to the controller 25, and a sensor 30 coupledto the controller 25. The laser subsystem 28 outputs and scans a pulsedlaser beam at a desired target (e.g., corneal tissue) in response to thecontroller 25. In addition to managing the operation of the lasersubsystem 28 (e.g., beam scanning, scan rate, focal spot depth variationof the pulsed laser beam, and the like), the controller 25 establishesthe properties/characteristics of the pulsed laser beam (e.g., pulseenergy setting, pulse width setting, and the like). One example of anophthalmic laser surgery system where the system 23 may be implementedis described in U.S. Pat. No. 7,027,233, the entire disclosure of whichis incorporated herein.

The controller 25 includes computer hardware and/or software, oftenincluding one or more programmable processor unit running machinereadable program instructions or code for implementing some or all ofone or more of the methods described herein. In one embodiment, the codeis embodied in a tangible media such as a memory (optionally a read onlymemory, a random access memory, a non-volatile memory, or the like)and/or a recording media (such as a floppy disk, a hard drive, a CD, aDVD, a memory stick, or the like). The code and/or associated data andsignals may also be transmitted to or from the controller 25 via anetwork connection (such as a wireless network, an Ethernet, aninternet, an intranet, or the like), and some or all of the code mayalso be transmitted between components of the system 23 and within thecontroller 25 via one or more bus, and appropriate standard orproprietary communications cards, connectors, cables, and the like canbe included in the controller 25.

The controller 25 is preferably configured to perform the calculationsand signal transmission steps described herein at least in part byprogramming the controller 25 with the software code, which may bewritten as a single program, a series of separate subroutines or relatedprograms, or the like. The controller 25 may include standard orproprietary digital and/or analog signal processing hardware, software,and/or firmware, and has sufficient processing power to perform thecalculations described herein during treatment of the patient. Thecontroller 25 optionally includes a personal computer, a notebookcomputer, a tablet computer, a proprietary processing unit, or acombination thereof. Standard or proprietary input devices (such as amouse, keyboard, touchscreen, joystick, etc.) and output devices (suchas a printer, speakers, display, etc.) associated with modern computersystems may also be included, and processors having a plurality ofprocessing units (or even separate computers) may be employed in a widerange of centralized or distributed data processing architectures.

In a first mode, the controller 25 and laser subsystem 28 provideprecision depth measurements (i.e., using a pulse energy setting belowthe photoalteration threshold of the tissue) without photoaltering thecorneal tissue. Although the system 23 has a non-photoaltering mode, thesystem 23 can also be a surgical instrument. For example, in a secondmode, the controller 25 and laser subsystem 28 photoalter tissue inaccordance with a desired ophthalmic procedure (e.g., corneal flapincision, LASIK, PRK, LASEK, corneal transplant, and the like). Thecontroller 25 and laser subsystem 28 may operate in both modessimultaneously (e.g., providing real time depth measurement, laser beamfocal spot depth calibration, and the like) or seamlessly alternatebetween the two modes.

To provide the pulsed laser beam, the laser subsystem 38 may use achirped pulse laser amplification system, such as described in U.S. Pat.No. RE37,585. Other devices or systems may be used to generate pulsedlaser beams. For example, non-ultraviolet (UV), ultrashort pulsed lasertechnology can produce pulsed laser beams having pulse durationsmeasured in femtoseconds. U.S. Pat. Nos. 4,764,930 and 5,993,438, theentire disclosures of which are incorporated herein, disclose devicesfor performing ophthalmic surgical procedures to effect high-accuracycorrections of optical aberrations. The laser subsystem 28 is capable ofgenerating a pulsed laser beam with characteristics similar to those ofthe laser beams generated by a laser system disclosed in U.S. Pat. No.4,764,930, U.S. Pat. No. 5,993,438, or the like.

For example, the system 23 can produce a non-UV, ultrashort pulsed laserbeam for use as an incising laser beam. This pulsed laser beampreferably has laser pulses with durations as long as a few nanosecondsor as short as a few femtoseconds. The pulsed laser beam has awavelength that permits propagation through the cornea withoutabsorption by the corneal tissue, except at the focal spot of the pulsedlaser beam. The wavelength of the pulsed laser beam is generally in therange of about 3 μm to about 1.9 nm, and preferably between about 400 nmto about 3000 nm. For depth measurement, the irradiance of the pulsedlaser beam is preferably less than the threshold for optical breakdownof the tissue. For accomplishing photodisruption of stromal tissues atthe focal spot or for incising corneal tissue in general (e.g., in thesecond mode), the irradiance of the pulsed laser beam is selected to begreater than the threshold for optical breakdown of the tissue. Althougha non-UV, ultrashort pulsed laser beam is described in this embodiment,the pulsed laser beam may have other pulse durations and differentwavelengths in other embodiments.

Scanning by the laser subsystem 28 is accomplished under direction ofthe controller 25 to selectively move the focal spot of the laser beam.The laser subsystem 28 can operate at scan rates between about 10 kHzand about 400 kHz, or at any other desired scan rate. Further details oflaser scanning are known in the art, such as described, for example, inU.S. Pat. No. 5,549,632, the entire disclosure of which is incorporatedherein by reference. For example, a pair of scanning mirrors or otheroptics may be used to angularly deflect and scan one or more inputbeams. The scanning mirrors may be driven by galvanometers such thateach of the mirrors scans along different orthogonal axes (e.g., anx-axis and a y-axis). A focusing objective (not shown), having one ormore lenses, images the input beam onto a focal plane of the system 23.The focal spot may thus be scanned in two dimensions (e.g., along thex-axis and the y-axis) within the focal plane of the system 23. Scanningalong the third dimension, i.e., moving the focal plane along an opticalaxis (e.g., a z-axis), may be achieved by moving a focusing objective,or one or more lenses within the focusing objective, along the opticalaxis.

The system 23 may additionally acquire detailed information aboutoptical aberrations to be corrected or verify/correlate the depthmeasurements with such detailed information (e.g., data registration).Examples of such detailed information include, but are not necessarilylimited to, refractive power maps of the cornea, corneal topography,iris registration information, and the like. Wavefront analysistechniques, made possible by devices such as a Hartmann-Shack typesensor, can be used to generate maps of corneal refractive power, andoptical coherence tomography may be used to generate corneal topographs.Other wavefront analysis techniques and sensors may also be used.

During the first mode, the laser subsystem 28 outputs a pulsed laserbeam having predetermined properties associated with the generation of anonlinear frequency signal based on the pulsed laser beam (e.g., anon-primary harmonic of the pulsed laser beam such as a second harmonicgeneration, a third harmonic generation, stimulated Raman, white lightgeneration, and the like) during propagation of the pulsed laser beam inthe cornea 12. On example of harmonic signal generation based on a laserbeam is disclosed in U.S. Pat. No. 6,992,765. In this patent, a methodis disclosed for determining the depth of focus of a laser beam inrelation to the plane of an aplanation lens by monitoring a nonlinearfrequency signal generated by the laser beam, the disclosure of which isincorporated herein. A change in the signal indicates the interfacebetween lower surfaces of the aplanation glass and the cornea.

The systems, apparatus, and methods of the present invention haveadvanced, inter alia, the detection of a nonlinear frequency signalgenerated by the laser beam. In particular, the systems, apparatus, andmethods of the present invention detect and identify corneal tissuetransitions based the detection of a nonlinear frequency signalgenerated by a pulsed laser beam propagating in corneal tissue. Forexample, the wavelength of the pulsed laser beam can be selected suchthat an intensity of the nonlinear frequency signal correlates with thetissue density and type. The nonlinear frequency signal abruptly changescharacteristics at a corneal tissue layer transition (e.g., from theepithelium 14 to Bowman's layer 16, from Bowman's layer 16 to stroma 18,from stroma 18 to Descemet's membrane 20, etc.). In one embodiment, anoptimal wavelength is selected to maximize this change and enhance thedetection of one or more corneal tissue layer transitions.

As previously mentioned, incisions to access the stroma 18 arepreferably located so as to maximize the amount of stroma for refractivecorrection (e.g., ablation and the like). For example, the incision isproximally located adjacent to Bowman's layer 16 to maximize the amountof stroma for refractive correction. In one embodiment, the depth ofBowman's layer 16 is precisely determined in the first mode, and thecornea 12 is incised at a depth below Bowman's layer 16 (e.g., to form aflap bed associated with the corneal flap) in the second mode.

For a precision depth measurement (e.g., the depth of Bowman's layer orother corneal tissue layers), the pulsed laser beam is focused to afocal spot with an energy less than the threshold for optical breakdownof the tissue, and the focal spot is scanned at various depths withinthe cornea 12. For example, the focal spot is scanned along the opticalaxis (e.g., z-axis), which may be normal to the anterior surface of thecornea or aligned in accordance with a pre-determined scan pattern. Inone experiment, a pulsed laser beam with an energy level of about 0.2 μJwas directed into the cornea so that the corresponding fluence was lessthan the optical damage threshold (see U.S. Pat. No. 6,992,765 for someexamples of other energy levels that are less than the optical damagethreshold of the cornea).

As the focal spot is scanned in the cornea 12, a harmonic of the beam isgenerated in the corneal tissue (e.g., a green harmonic wavelength orthe like). For example, a second harmonic is generated in the cornealtissue based on a primary wavelength of the pulsed laser beam. Thesensor 30 (e.g., a photodetector) detects and measures the harmonicgenerated by the propagation of the pulsed laser beam in the cornea 12.In one embodiment, the sensor 30 is configured to receive the harmonicusing an optical bandpass filter with a filter bandwidth sufficient fordetecting the harmonic wavelength, although other sensing devices may beused to detect the harmonic.

One or more parameters of the pulsed laser beam (e.g., pulse width,wavelength, energy, and the like) may be selected such that the detectedharmonic indicates an optimal change in intensity at a tissue layertransition. Additionally, one or more of the pulsed laser beamparameters may be selected such that different predetermined changes inintensity (i.e., of the detected harmonic) are produced correspondingwith different tissue laser transitions. For example, the pulsed laserbeam parameter(s) may be selected such that a first intensity change inthe detected harmonic corresponds with a transition from the epithelium14 to Bowman's layer 16, a second intensity change in the detectedharmonic corresponds with a transition from Bowman's layer 16 to stroma18, a third intensity change in the detected harmonic corresponds with atransition from stroma 18 to Descemet's membrane 20, and a fourthintensity change in the detected harmonic corresponds with a transitionfrom Descemet's membrane 20 to the endothelium 22. Other tissue layertransitions (e.g., associated with the cornea 12 or other tissues orstructures of the eye 10) may be earmarked for identification based onthe detected harmonic and/or by selection of an appropriate pulsed laserbeam wavelength.

As shown in FIG. 1, in one embodiment, the laser subsystem 28 directs apulsed laser beam 31A, 31B, 31C at the cornea 12 and scans the tissuelayer depth at varying focal spot positions. Three pulsed laser beams31A, 31B, 31C are described for convenience of illustrating the varietyof placements of the focal spot. For example, a first pulsed laser beam31A can be focused at focal spot position A, a second pulsed laser beam31B can be focused at focal spot position B, and a third pulsed laserbeam 31C can be focused at a focal spot position C. Position A is at thesurface of the epithelium 14, position B is at the transition betweenthe epithelium 14 and Bowman's layer 16, and position C is in the stroma18. In another embodiment, a single beam is directed into the cornea 12at the focal spot positions A, B, C or to other different focal spotpositions. The focal spot position of the pulsed laser beam may also becontinuously varied or incrementally varied (e.g., by predeterminedfocal spot displacements).

The identification of the tissue layer transition(s) can be used tocalibrate the incision depth of the pulsed laser beam before or duringrefractive surgery procedures. In one embodiment, the system 23 includesa Z-encoder module 27 coupled to the controller 25 and sensor 30, andthe Z-encoder module registers the focal spot position (e.g., focal spotdepth) of the pulsed laser beam with the corresponding detected tissuelayer transition. For example, the Z-encoder module 27 may include alinear encoder having an encoder strip (e.g., a glass strip with areflective gradient), a sensor head, and an interpolator-to-serialmodule that indicates the position of the focusing objective or otherz-focus assembly. The Z-encoder module 27 preferably has a resolution ofabout 0.1 microns or less per count at a frequency of about 900 MHz orgreater. With the encoder strip coupled to the focusing objective, theposition of focusing objective or z-focus assembly can be determinedusing the linear encoder, and the focal spot position can be controlledto within a few microns of a predetermined absolute value. Correlatingthis information with the detected harmonic signal, the focal spotposition can be verified and the laser subsystem 28 can be calibrated.This can be used to precisely locate incisions and produce thin cornealflaps, as well as other flap configurations. For example, corneal flapbeds can be located in the range of about 20 microns below theepithelium/Bowman's layer tissue transition.

In addition to real-time calibration of the laser subsystem 28, thedetection of tissue layer transitions can be used for two- orthree-dimensional corneal mapping and the like. For example, an array ofthe depth measurements over an area of corneal tissue may be used toidentify the anatomical layers of the cornea 12, determine the thicknessof one or more of such layers, and the like. A variety of scan patternsmay be used to obtain multiple depth measurements across the cornea.

FIG. 2 is a graph of intensity versus focal spot position (e.g., focalspot depth along an optical axis) illustrating a relationship ofintensity change in a detected harmonic signal as a function of focalspot depth of a pulsed laser beam propagating within corneal tissue inaccordance with one embodiment. The intensity and focal spot positionare in arbitrary units (a.u.). To obtain the relationship shown in FIG.2, the focal spot of the pulsed laser beam (e.g., the pulsed laser beam31A, 31B, 31C, which may be produced by the system 23 show in FIG. 1) isscanned along an optical axis at varying depths of the corneal tissue,and the harmonic signal is detected (e.g., using the sensor 30 shown inFIG. 1). As the focal spot of the pulsed laser beam propagates throughthe corneal tissue, the intensity of the harmonic signal varies based onthe corneal tissue thickness and type. For example, the slope of a firstsegment 34 represents an intensity change of the harmonic signal as thefocal spot position of the pulsed laser beam propagates through theepithelium, the slope of a second segment 36 represents an intensitychange of the harmonic signal as the focal spot position of the pulsedlaser beam propagates through Bowman's layer, and the slope of a thirdsegment 38 represents the intensity change of the harmonic signal as thefocal spot position of the pulsed laser beam propagates through thestroma. The intensity may be a nonlinear interference frequency signalbased on the pulsed laser beam, such as a second harmonic generation, athird harmonic generation, a stimulated Raman, a white light generation,or other suitable optical signals.

The position of a transition between corneal tissue layers can beidentified by the detection (e.g., via the controller 25) of an abruptchange in the harmonic signal at the transition. For example, in FIG. 2,the epithelium/bowman's transition occurs at a first abrupt change 40,and the Bowman's layer/stroma transition occurs at a second abruptchange 42. The abrupt change can be predetermined based on historicalinformation, corneal tissue models, and the like, for example. Thedistance between these abrupt changes may also be used to determine thethickness of a particular layer. For example, the thickness of Bowman'slayer corresponds with the distance between the first abrupt change 40and the second abrupt change 42. A position beyond the second abruptchange 42 (shown by arrow 44) is within the stroma. Other graphs mayalso be prepared illustrating other tissue layer transitions (e.g., froma posterior surface of the cornea or for other structures of the eye)based on corresponding relationships of intensity change in the detectedharmonic signal as a function of focal spot depth of the pulsed laserbeam.

FIG. 3 is a schematic diagram of a laser system 50 in accordance withanother embodiment. While FIG. 1 shows one embodiment of a laser system23 directing a pulsed laser beam directly into the cornea 12, FIG. 3shows another embodiment of a laser system 50 used in situ and while thecornea 12 is in contact with an aplanation lens 54. The laser system 50can be substantially similar to the laser system 23 (shown in FIG. 1)with the additional component of the aplanation lens 54. The aplanationlens 54 can be a flat or curved contact glass with a predeterminedthickness, which can provide a reference for thickness measurements ofvarious layers of the cornea 12 or other features of the eye. Examplesof aplanation lenses include, by way of example and not limitation, U.S.Pat. No. 6,254,595, U.S. Pat. No. 6,863,667, U.S. Pat. No. 6,899,707,U.S. Pat. Publication No. 20050192562, and U.S. Pat. Publication No.20070093795. In detecting corneal tissue transitions, the thickness ofthe aplanation lens 54 is included as a reference depth.

The laser system 50 directs the focal point of a pulsed laser beam 52through the aplanation lens and into the cornea 12 along the opticalaxis (e.g., the z-axis). In this embodiment, the laser system 50 isshown scanning the pulsed laser beam 52 along the z-axis in the cornea12 to detect the transition between the epithelium 14 and Bowman's layer16. Other corneal tissue layer transitions may also be determined withthe pulsed laser beam 52 directed through the aplanation lens 54. Aprecision Z-calibration can also be performed with the laser system 50in real time during an ophthalmic procedure on the eye.

FIG. 4 is a top view of a corneal flap mapped onto the cornea 12 inaccordance with one embodiment. As previously mentioned, precision depthmeasurements (e.g., using the system 23 shown in FIG. 1 or the system 50shown in FIG. 3) may be taken at various locations across the cornea 12to create a three-dimensional map of the cornea 12. In this embodiment,Z-calibrated depth measurements are used to determine a precision flapzone 60 from which the system 23, 50 can create a three-dimensional flapmap (e.g., with precision on the micron order). The three-dimensionalflap map preferably displays the flap incision below the bowman's/stromainterface.

FIG. 5 is a block diagram of a laser system 100 in accordance withanother embodiment. In this embodiment, the laser system 100 includes alaser 102 that outputs a pulsed laser beam for mapping corneal layersand for incising the cornea (e.g., to form a corneal flap, a lenticule,a corneal graft, and the like), a beam splitting device 104, a z-scanner110, and a focusing objective 112 (e.g., a focusing lens). The laser 102may be a femtosecond laser that produces a pulsed laser beam 103, aspreviously described. The pulsed laser beam 103 is directed to the beamsplitting device 104, which divides the pulsed laser beam 103 into afirst beam 106 and a second beam 108.

The first beam 106 is a diagnostic beam having focused energies lessthan the photodisruption threshold of the cornea 12 and is used forcorneal mapping to identify the different layers within the cornea 12.For example, by varying the focal spot position of the beam 106 acrossthe cornea 12 using the scanner 110 and varying the focal spot depthusing the z-scanner 110, the first beam 106 is scanned through thecornea 12 to detect the harmonic of the laser beam wavelength. Theharmonic of the first beam 106 is used to determine one or more tissuelayer transitions within the cornea 12 (e.g., between Bowman's layer andstroma) based on a predetermined change in the harmonic as the beam 106propagates in the corneal tissue. The first beam 106 can also be used todetermining a distance from an anterior surface of the cornea 12 to thetransition between Bowman's layer and stroma. A buffer depth may beadded to this determined distance to provide a planned incision depththat ensures the incision of the corneal flap in the stroma. This bufferdepth may range between about 10 and about 40 microns.

The second beam 108 is a surgical beam having focused energies greaterthan the photodisruption threshold of the cornea 12 and can incise aflap below the Bowman's layer/stroma transition. In some embodiments,the second beam 108 is also used for shaping the stroma (e.g., after theflap is lifted to reveal the flap bed or intrastromally without creatinga flap or with the cornea intact). By dividing the beam 104 into twobeams 106, 108, the laser system 100 allows a diagnostic beam to be usedin real time during an ophthalmic procedure, which providesinstantaneous Z control of the surgical beam.

In any of the embodiments, the system 100 may include a processor (e.g.,the controller 25 shown in FIG. 1) to control various functions of thesystem, for example, control a Z-encoder (e.g., the Z-encoder module 27shown in FIG. 1) or the scanner 110, vary the focal spot position of thebeam, process focal spot position information, and the like. Theprocessor may also be coupled to a sensor (e.g., the sensor 30 shown inFIG. 1) that measures the emitted harmonic from the tissue. In thisexample, the processor determines a tissue layer transition betweenBowman's layer and the stroma based on a detected predetermined changein the harmonic (of the laser wavelength) in the cornea tissue anddetermines a distance from an anterior surface to the transition. Theprocessor may also incorporate the buffer depth to this determineddistance to provide the planned incision depth.

FIG. 6 is a cross-sectional view of a portion of the eye 10 showing adiagnostic beam, such as the first beam 106 shown in FIG. 5, scanningthe cornea 12. The transition between Bowman's layer 16 and the stroma18 is identified by varying the focal spot depth of the diagnostic beam106 (e.g., along the optical axis or the z-axis). A distance can bedetermined between the tissue layer transition and the anterior surfaceof the cornea 12. FIG. 7 is a cross-sectional view of a portion of theeye 10 showing a surgical beam, such as the second beam 108 shown inFIG. 5, incising a flap 120 in the stroma below the transition betweenBowman's layer 16 and the stroma 18. The flap 120 can be folded back toexpose the stroma 18 for further treatment. As shown by FIGS. 5-7, asingle laser may be used to produce both the diagnostic beam and thesurgical beam and direct one or both of the beams at the eye.

The methods and system 23, 50, 100 described above allow a femtosecondlaser to precisely locate incisions and incise extremely thin, precise,accurate, custom corneal flaps. The laser system 23, 50, 100 can also beused as a combined precision measurement tool and ophthalmic surgicalinstrument.

While the disclosure has been described in connection with specificembodiments thereof, it will be understood that it is capable of furthermodifications. This application is intended to cover any variations,uses, or adaptations of the disclosure following, in general, thedisclosed principles and including such departures from the disclosureas come within known or customary practice within the art to which thedisclosure pertains and as may be applied to the essential featureshereinbefore set forth.

1-26. (canceled)
 27. A method of locating tissue layers within a cornea,the cornea having an anterior surface, a posterior surface, and aphotodisruption threshold, the method comprising the steps of generatinga laser beam from a femtosecond laser, the laser beam having awavelength between 400 nm to 3000 nm; focusing the laser beam to a laserspot having an energy level such that the irradiance of the laser spotis below the photodisruption threshold of the cornea; varying a positionof the laser spot between the anterior surface of the cornea and theposterior surface of the cornea, a harmonic signal being produced as thelaser spot propagates in the cornea wherein the harmonic signal has anintensity correlated with a density of the cornea; and determining atransition of the tissue layers based on a predetermined change in theharmonic signal, the predetermined change comprising a change in theintensity of the harmonic signal.
 28. The method of claim 1, furthercomprising determining a depth measurement from the anterior surface ofthe cornea or the posterior surface of the cornea based on thetransition of tissue layers.
 29. The method of claim 1, furthercomprising determining a thickness between a first tissue layer of thetissue layers and a second tissue layer of the tissue layers based onthe transition of the tissue layers.
 30. The method of claim 1, whereinthe tissue layers comprise one or more of the group consisting of anepithelium, a Bowman's layer, a stroma, a Descemet's membrane, and anendothelium.
 31. The method of claim 1, wherein the varying stepcomprises continuously varying a position of the laser spot between theanterior surface of the cornea and the posterior surface of the cornea.32. The method of claim 1, wherein the varying step comprises varying aposition of the laser spot in increments between the anterior surface ofthe cornea and the posterior surface of the cornea.
 33. The method ofclaim 1, further comprising determining multiple transitions of thetissue layers at various locations across the cornea.
 34. The method ofclaim 1, further comprising generating a three dimensional model of thetissue layers.
 35. The method of claim 1, further comprising applanatingthe cornea prior to determining the transition of tissue layers.
 36. Themethod of claim 1, further comprising calibrating a focal depth of thelaser spot based on the transition of the tissue layers.
 37. Anapparatus for determining a depth measurement and incising a cornea, thecornea having a photodisruption threshold, the apparatus comprising: afirst input operable to receive a first input signal indicating a focaldepth of a laser beam within the cornea, the laser beam having an energybelow the photodisruption threshold; a second input operable to receivea second input signal representing a harmonic of the laser beamgenerated as the laser beam propagates in the cornea; an output; and aprocessor coupled to the first input, the second input, and the output,the processor configured to: detect a pre-determined change in thesecond input signal, the pre-determined change indicating a tissue layerinterface within the cornea; correlate the focal depth of the laser beamwith the tissue layer transition to provide a reference depth of thelaser beam; and transmit an output signal via the output, the outputsignal indicating the reference depth of the laser beam.
 38. Theapparatus of claim 22, wherein the cornea has a Bowman's layer, astroma, and an epithelium, and wherein the processor is furtherconfigured to: determine a first tissue layer transition between theBowman's layer and the stroma based on a first pre-determined change inthe second input signal; and determine a second tissue layer transitionbetween the Bowman's layer and the epithelium based on a secondpre-determined change in the second input signal.
 39. The apparatus ofclaim 22, wherein the cornea has an anterior surface and a posteriorsurface, and wherein the processor is further configured to determine adistance from an anterior surface of the cornea to the tissue layertransition.
 40. The apparatus of claim 24, wherein the cornea has astroma, and wherein the processor is further configured to determine anincision depth of the laser beam based on the tissue layer transition,the incision depth being within the stroma.
 41. The apparatus of claim24, wherein the processor is further configured to: determine multipletissue layer transitions in the cornea based by detecting differentpre-determined changes in the second input signal; and generate a threedimensional model based on the multiple tissue layer transitions.